Search results for: drug stability

Authors: Obinna Emmanuel Ezenkwa, Sani Amril Samsudin, Azman Hassan, Ede Anthony

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A major challenge of polypropylene (PP) in high-heat application areas is its poor thermal stability. Under high temperature, PP burns readily with high degradation temperature and can self-ignite. In this study, PP is reinforced with hybrid filler of graphene (xGNP) and rice husk (RH) with RH at 15 wt%, and xGNP varied at 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0 parts per hundred (phr) of the composite. Compatibilizer MAPP was also added in each sample at 4phr of the composite. Sample formulations were melt-blended using twin screw extruder and injection moulding machine. At xGNP optimum content of 1.5 phr, hybrid PP/RH/G1.5/MAPP nanocomposite increased in thermal stability by 24 °C and 30 °C compared to pure PP and unhybridized PP/RH composite respectively; char residue increased by 513% compared to pure PP and degree of crystallization (Xc) increased from 35.4% to 36.4%. The observed thermal properties enhancement in the hybrid nanocomposites can be related to the high surface area, gap-filling effect and exfoliation characteristics of the graphene nanofiller which worked in synergy with rice husk fillers in reinforcing PP. This study therefore, shows that graphene nanofiller inclusion in polymer composites fabrication can enhance the thermal stability of polyolefins for high heat applications.

Keywords: polymer nanocomposites, thermal stability, exfoliation, hybrid fillers, polymer reinforcement

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Authors: Natida Thongsima, Patompong Satapornpong

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Introduction: Lamotrigine is widely used in the treatment of epilepsy and bipolar disorder. However, lamotrigine leads to adverse drug reactions (ADRs) consist of severe cutaneous adverse reactions (SCARs) include Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug rash with eosinophilia and systemic symptoms (DRESS). Moreover, lamotrigine-induced SCARs are usually manifested between 2 and 8 weeks after treatment initiation. According to a previous study, the association between HLA-B*15:02 and lamotrigine-induced cutaneous adverse drug reactions in the Thai population (odds ratio 4.89; 95% CI 1.28–18.66; p-value = 0.014) was found. Therefore, the distribution of pharmacogenetics markers a major role in predicting the culprit drugs for SCARs in many populations. Objective: In this study, we want to investigate the prevalence of HLA-B allele, which correlates with lamotrigine-induced SCARs in the healthy Thai population. Materials and Methods: We enrolled 350 healthy Thai individuals and were approved by the ethics committee of Rangsit University. HLA-B alleles were genotyped by the Lifecodes HLA SSO typing kits (Immucor, West Avenue, Stamford, USA). Results: The results presented HLA-B allele frequency in healthy Thai population were 14.71% (HLA-B*46:01), 8.57% (HLA-B*15:02), 6.71% (HLA-B*40:01), 5.86% (HLA-B*13:01), 5.71% (HLA-B*58:01), 5.14% (HLA-B*38:02), 4.86% (HLA-B*18:01), 4.86% (HLA-B*51:01), 3.86% (HLA-B*44:03) and 2.71% (HLA-B*07:05). Especially, HLA-B*15:02 allele was the high frequency in the Thais (8.57%), Han Chinese (7.30%), Vietnamese (13.50%), Malaysian (6.06%) and Indonesian (11.60%). Nevertheless, this allele was much lower in other populations, namely, Africans, Caucasians, and Japanese. Conclusions: Although the sample size of the healthy Thai population in this research was limited, there were found the frequency of the HLA-B*15:02 allele could predispose them toward to lamotrigine-induced SCARs in Thailand.

Keywords: lamotrigine, cutaneous adverse drug reactions, HLA-B, Thai population

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Authors: Biruk Wolde Eremacho

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The Kombolcha to Desse road, linking Addis Ababa with Northern Ethiopia towns traverses through one of the most difficult mountainous ranges in Ethiopia. The presence of loose unconsolidated materials (colluvium materials), highly weathered and fractured basalt rocks high relief, steep natural slopes, nature of geologic formations exposed along the road section, poor drainage conditions, occurrence of high seasonal rains, and seismically active nature of the region created favorable condition for slope instability in the area. Thus, keeping in mind all above points the present study was conceived to study in detail the slope stability condition of the area. It was realized that detailed slope stability studies along this road section are very necessary to identify critical slopes and to provide the best remedial measures to minimize the slope instability problems which frequently disrupt and endanger the traffic movement on this important road. For the present study based on the field manifestation of instability two most critical slope sections were identified for detailed slope stability analysis. The deterministic slope stability analysis approach was followed to perform the detailed slope stability analysis of the selected slope sections. Factor of safety for the selected slope sections was determined for the different anticipated conditions (i.e., static and dynamic with varied water saturations) using Slope/W and Slide software. Both static and seismic slope stability analysis were carried out and factor of safety was deduced for each anticipated conditions. In general, detailed slope stability analysis of the two critical slope sections reveals that for only static dry condition both the slopes sections would be stable. However, for the rest anticipated conditions defined by static and dynamic situations with varied water saturations both critical slope sections would be unstable. Moreover, the causes of slope instability in the study area are governed by different factors; therefore integrated approaches of remedial measures are more appropriate to mitigate the possible slope instability in the study area. Depending on site condition and slope stability analysis result four types of suitable preventive and remedial measures are recommended namely; proper managements of drainages, retaining structures, gabions, and managing steeply cut slopes.

Keywords: factor of safety, remedial measures, slope stability analysis, static and dynamic condition

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Authors: K. Radha Krishnan, Mirajul Alom

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Dehydrated powder prepared from fresh radish (Raphanus sativus) leaves were investigated for the color stability by different drying methods (tray, sun and solar). The effect of blanching conditions, drying methods as well as drying temperatures (50 – 90°C) were considered for studying the color degradation kinetics of chlorophyll in the dehydrated powder. The hunter color parameters (L*, a*, b*) and total color difference (TCD) were determined in order to investigate the color degradation kinetics of chlorophyll. Blanching conditions, drying method and drying temperature influenced the changes in L*, a*, b* and TCD values. The changes in color values during processing were described by a first order kinetic model. The temperature dependence of chlorophyll degradation was adequately modeled by Arrhenius equation. To predict the losses in green color, a mathematical model was developed from the steady state kinetic parameters. The results from this study indicated the protective effect of blanching conditions on the color stability of dehydrated radish powder.

Keywords: chlorophyll, color stability, degradation kinetics, drying

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Authors: Nasser A. M. Habib

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The impressive physical properties of graphene derivatives, including thermal properties, have made them an attractive addition to advanced construction nanomaterial. In this study, we investigated the impact of incorporating low amounts of graphene oxide (GO) into cement mixture nanocomposites on their heat storage and thermal stability. The composites were analyzed using Fourier transmission infrared, thermo-gravimetric analysis, and field emission scanning electron microscopy. Results showed that GO significantly improved specific heat by 30%, reduced thermal conductivity by 15%, and reduced thermal decomposition to only 3% at a concentration of 1.2 wt%. These findings suggest that the cement mixture can withstand high temperatures and may be suitable for specific applications requiring thermal stability and insulation properties.

Keywords: cement mixture composite, graphene oxide, thermal decomposition, thermal conductivity

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Authors: Soad Ali Yehia, Mohamed Shafik El-Ridi, Mina Ibrahim Tadros, Nolwa Gamal El-Sherif

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Fexofenadine hydrochloride (FXD) is a slightly soluble, bitter-tasting, drug having an oral bioavailability of 35%. The maximum plasma concentration is reached 2.6 hours (Tmax) post-dose. The current work aimed to develop taste-masked FXD orodispersible tablets (ODTs) to increase extent of drug absorption and reduce Tmax. Taste masking was achieved via solid dispersion (SD) with chitosan (CS) or sodium alginate (ALG). FT-IR, DSC and XRD were performed to identify physicochemical interactions and FXD crystallinity. Taste-masked FXD-ODTs were developed via addition of superdisintegrants (crosscarmelose sodium or sodium starch glycolate, 5% and 10%, w/w) or sublimable agents (camphor, menthol or thymol; 10% and 20%, w/w) to FXD-SDs. ODTs were evaluated for weight variation, drug-content, friability, wetting time, disintegration time and drug release. Camphor-based (20%, w/w) FXD-ODT (F12) was optimized (F23) by incorporation of a more hydrophilic lubricant, sodium stearyl fumarate (Pruv®). The topography of the latter formula was examined via scanning electron microscopy (SEM). The in vivo estimation of FXD pharmacokinetics, relative to Allegra® tablets, was evaluated in healthy human volunteers. Based on the gustatory sensation test in healthy volunteers, FXD:CS (1:1) and FXD:ALG (1:0.5) SDs were selected. Taste-masked FXD-ODTs had appropriate physicochemical properties and showed short wetting and disintegration times. Drug release profiles of F23 and phenylalanine-containing Allegra® ODT were similar (f2 = 96) showing a complete release in two minutes. SEM micrographs revealed pores following camphor sublimation. Compared to Allegra® tablets, pharmacokinetic studies in healthy volunteers proved F23 ability to increase extent of FXD absorption (14%) and reduce Tmax to 1.83 h.

Keywords: fexofenadine hydrochloride, taste masking, chitosan, orodispersible

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Authors: Malik Shahzad Shabbir, Muhammad Saarim Ghazi, Amir Khalil ur Rehman

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This study examines the factors which influence and contribute towards the financial viability of Islamic finance and its impact on global financial stability. However, the purpose of this paper is to differentiate the practical implications of both Islamic and conventional finance on global financial stability. The Islamic finance is asset backed financing which creates wealth through trade, commerce and believes in risk and return sharing. Islamic banking is asset driven as against to conventional banking which is liability driven. In order to introduce new financial products for market, financial innovation in Islamic finance must be within the Shari’ah parameters that are tested against the ‘Maqasid al-Shari’ah’. Interest-based system leads to income and wealth inequalities and mis-allocation of resources. Moreover, this system has absence of just and equitable aspect of distribution that may exploit either the debt holder or the financier. Such implications are reached to a tipping point that leaves only one choice: change or face continued decline and misery.

Keywords: viability, global financial stability, practical implications, asset driven, tipping point

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Authors: Neslihan Demirci, Serdar Durdağı

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Mycobacterium tuberculosis is still a worldwide disease-causing agent that, according to WHO, led to the death of 1.5 million people from tuberculosis (TB) in 2020. The bacteria reside in macrophages located specifically in the lung. There is a known quadruple drug therapy regimen for TB consisting of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Over the past 60 years, there have been great contributions to treatment options, such as recently approved delamanid (OPC67683) and bedaquiline (TMC207/R207910), targeting mycolic acid and ATP synthesis, respectively. Also, there are natural compounds that can block the tryptophanyl-tRNA synthetase (TrpRS) enzyme, chuangxinmycin, and indolmycin. Yet, already the drug resistance is reported for those agents. In this study, the newly released TrpRS enzyme structure is investigated for potential inhibitor drugs from already synthesized molecules to help the treatment of resistant cases and to propose an alternative drug for the quadruple drug therapy of tuberculosis. Maestro, Schrodinger is used for docking and molecular dynamic simulations. In-house library containing ~8000 compounds among FDA-approved indole-containing compounds, a total of 57 obtained from the ChemBL were used for both ATP and tryptophan binding pocket docking. Best of indole-containing 57 compounds were subjected to hit expansion and compared later with virtual screening workflow (VSW) results. After docking, VSW was done. Glide-XP docking algorithm was chosen. When compared, VSW alone performed better than the hit expansion module. Best scored compounds were kept for ten ns molecular dynamic simulations by Desmond. Further, 100 ns molecular dynamic simulation was performed for elected molecules according to Z-score. The top three MMGBSA-scored compounds were subjected to steered molecular dynamic (SMD) simulations by Gromacs. While SMD simulations are still being conducted, ponesimod (for multiple sclerosis), vilanterol (β₂ adrenoreceptor agonist), and silodosin (for benign prostatic hyperplasia) were found to have a significant affinity for tuberculosis TrpRS, which is the propulsive force for the urge to expand the research with in vitro studies. Interestingly, top-scored ponesimod has been reported to have a side effect that makes the patient prone to upper respiratory tract infections.

Keywords: drug repurposing, molecular dynamics, tryptophanyl-tRNA synthetase, tuberculosis

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Authors: Filip Dodigovic, Kreso Ivandic, Damir Stuhec, S. Strelec

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The general difference analysis between the former and new design concepts in geotechnical engineering is carried out. The application of new regulations results in the need for real adaptation of the computation principles of limit states, i.e. by providing a uniform way of analyzing engineering tasks. Generally, it is not possible to unambiguously match the limit state verification procedure with those in the construction engineering. The reasons are the inability to fully consistency of the common probabilistic basis of the analysis, and the fundamental effect of material properties on the value of actions and the influence of actions on resistance. Consequently, it is not possible to apply separate factorization with partial coefficients, as in construction engineering. For the slope stability analysis design procedures problems in the light of the use of limit states in relation to the concept of allowable stresses is detailed in. The quantifications of the safety margins in the slope stability analysis for both approaches is done. When analyzing the stability of the slope, by the strict application of the adopted forms from the new regulations for significant external temporary and/or seismic actions, the equivalent margin of safety is increased. The consequence is the emergence of more conservative solutions.

Keywords: allowable pressure, Eurocode 7, limit states, slope stability

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Authors: Rostyslav Horbay, Nick Korolis, Vahid Anvari, Rostyslav Stoika

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Introduction: Giant cancer cells (GCC) are common in all types of cancer, especially after poor therapy. Some specific features of such cells include ~10-fold enlargement, drug resistance, and the ability to propagate similar daughter cells. We used murine NK/Ly lymphoma, an aggressive and fast growing lymphoma model that has already shown drastic changes in GCC comparing to parental cells (chromatin condensation, nuclear fragmentation, tighter OXPHOS/cellular respiration coupling, multidrug resistance). Materials and methods: In this study, we compared morpho-functional changes of GCC that predominantly show either a cytostatic or a cytotoxic effect after treatment with drugs. We studied the effect of a combined cytostatic/cytotoxic drug treatment to determine the correlation of drug efficiency and GCC formation. Doses of G1/S-specific drug paclitaxel/PTX (G2/M-specific, 50 mg/mouse), vinblastine/VBL (50 mg/mouse), and DNA-targeting agents doxorubicin/DOX (125 ng/mouse) and cisplatin/CP (225 ng/mouse) on C57 black mice. Several tests were chosen to estimate morphological and physiological state (propidium iodide, Rhodamine-123, DAPI, JC-1, Janus Green, Giemsa staining and other), which included cell integrity, nuclear fragmentation and chromatin condensation, mitochondrial activity, and others. A single and double factor ANOVA analysis were performed to determine correlation between the criteria of applied drugs and cytomorphological changes. Results: In all cases of treatment, several morphological changes were observed (intracellular vacuolization, membrane blebbing, and interconnected mitochondrial network). A lower gain in ascites (49.97% comparing to control group) and longest lifespan (22+9 days) after tumor injection was obtained with single VBL and single DOX injections. Such ascites contained the highest number of GCC (83.7%+9.2%), lowest cell count number (72.7+31.0 mln/ml), and a strong correlation coefficient between increased mitochondrial activity and percentage of giant NK/Ly cells. A high number of viable GCC (82.1+9.2%) was observed compared to the parental forms (15.4+11.9%) indicating that GCC are more drug resistant than the parental cells. All this indicates that the giant cell formation and its ability to obtain drug resistance is an expanding field in cancer research.

Keywords: ANOVA, cisplatin, doxorubicin, drug resistance, giant cancer cells, NK/Ly lymphoma, paclitaxel, vinblastine

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Authors: Sudhir Kumar Singh, Debashish Chakravarty

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Slope stability analysis is an important aspect in the field of geotechnical engineering. It is also important from safety, and economic point of view as any slope failure leads to loss of valuable lives and damage to property worth millions. This paper aims at mitigating the risk of slope failure by studying the effect of different joint sets on the stability of mine pit slopes under the influence of various external factors, namely degree of saturation, rainfall intensity, and seismic coefficients. Supervised machine learning approach has been utilized for making accurate and reliable predictions regarding the stability of slopes based on the value of Factor of Safety. Numerous cases have been studied for analyzing the stability of slopes using the popular Finite Element Method, and the data thus obtained has been used as training data for the supervised machine learning models. The input data has been trained on different supervised machine learning models, namely Random Forest, Decision Tree, Support vector Machine, and XGBoost. Distinct test data that is not present in training data has been used for measuring the performance and accuracy of different models. Although all models have performed well on the test dataset but Random Forest stands out from others due to its high accuracy of greater than 95%, thus helping us by providing a valuable tool at our disposition which is neither computationally expensive nor time consuming and in good accordance with the numerical analysis result.

Keywords: finite element method, geotechnical engineering, machine learning, slope stability

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Authors: Mohammad Beyki, Justus Pawlak, Robert Patzke, Franz Renz

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In the context of planetary exploration, the MIMOS II (miniaturized Mössbauer spectrometer) serves as a proven and reliable measuring instrument. The transmission behaviour of the electronics in the Mössbauer spectroscopy is newly developed and optimized. For this purpose, the overall electronics is split into three parts. This elaboration deals exclusively with the first part of the signal chain for the evaluation of photons in experiments with gamma radiation. Parallel to the analysis of the electronics, a new method for the stability consideration of linear and non-linear systems is presented: The extended method of Lyapunov’s stability criteria. The design helps to weigh advantages and disadvantages against other simulated circuits in order to optimize the MIMOS II for the terestric and extraterestric measurment. Finally, after stability analysis, the controller design according to Ackermann is performed, achieving the best possible optimization of the output variable through a skillful pole assignment.

Keywords: Mössbauer spectroscopy, electronic signal amplifier, light processing technology, photocurrent, trans-impedance amplifier, extended Lyapunov method

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Authors: Mahdi Akhbardeh

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St John's wort plant can help to treat depression disease through decreasing this disease symptom, due to having some similar features of Prozac (Fluoxetine Hcl) pill. People suffering from slight depression who have fear of using antidepressants side effects can use St John's wort drops under doctor observation. This method of treatment is proposed specially to those women who are spending menopause or depression resulted from this period. St John's wort plant have proposed traditional and plant medicine as newest researches in treating mood disorders compared to Prozac (Fluoxetine Hcl) drug in treating depression disease which is being administrated in clinic research center of Washington. Objective: the aim of this study is to find an alternative treatment method in people suffering from depression which are treated with Prozac (Fluoxetine Hcl). Almost 70 percent of treatment failures with Prozac (Fluoxetine Hcl) drug in patients suffering from slight to normal depression is due to intensive side effects including: decrease in blood pressure, reduce in sexual desire and 30 percent of it is due to this drug affectless in treatment procedure which leads to leaving treatment. Results of Hypercuim plant function are exactly similar to antidepressants. Increase in serotonin amount in brain synopsis terminal end causes increase in existence time of this material in this part. In fact these two drugs have similar function. Though side effects of Hypercuim plant(St John's wort) including headache and slight nausea tolerable. Results: St John's wort plant can be used lonely in slight to normal depressions in which patients are avoiding Prozac (Fluoxetine Hcl) drug due to it's side effects. In intensive depressions through which general patients don’t indicate positive response to drug, it is probably expected relative or even complete treatment through combining antidepressants drugs with this plant. This treatment method has been investigated and confirmed in clinical tests and researches.

Keywords: depression, St John's wort, Prozac, antidepressant

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Authors: Michelle V. Tomczak, Reyhaneh Bakhtiari, Aaron Granley, Anthony Singhal

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Objective: Cannabis and cocaine are associated with a range of mental and physical effects that can impair aspects of human behavior. Driving is a complex cognitive behavior that is an essential part of everyday life and can be broken down into many subcomponents, each of which can uniquely impact road safety. With the growing movement of jurisdictions to legalize cannabis, there is an increased focus on impairment and driving. The purpose of this study was to identify driving-related cognitive-performance deficits that are impacted by recreational drug use. Design and Methods: With the assistance of law enforcement agencies, we recruited over 300 participants under the influence of various drugs including cannabis and cocaine. These individuals performed a battery of computer-based tasks scientifically proven to be re-lated to on-road driving performance and designed to test response-speed, memory processes, perceptual-motor skills, and decision making. Data from a control group with healthy non-drug using adults was collected as well. Results: Compared to controls, the drug group showed def-icits in all tasks. The data also showed clear differences between the cannabis and cocaine groups where cannabis users were faster, and performed better on some aspects of the decision-making and perceptual-motor tasks. Memory performance was better in the cocaine group for simple tasks but not more complex tasks. Finally, the participants who consumed both drugs performed most similarly to the cannabis group. Conclusions: Our results show distinct and combined effects of cannabis and cocaine on human performance relating to driving. These dif-ferential effects are likely related to the unique effects of each drug on the human brain and how they distinctly contribute to mental states. Our results have important implications for road safety associated with driver impairment.

Keywords: driving, cognitive impairment, recreational drug use, cannabis and cocaine

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Authors: Reza Hosseinpourpia, Stergios Adamopoulos, Carsten Mai

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Medium density fiberboard (MDF) is a common category of wood-based panels that are widely used in the furniture industry. Fine lignocellulosic fibres are combined with a synthetic resin, mostly urea formaldehyde (UF), and joined together under heat and pressure to form panels. Like solid wood, MDF is a hygroscopic material; therefore, its moisture content depends on the surrounding relative humidity and temperature. In addition, UF is a hydrophilic resin and susceptible to hydrolysis under certain conditions of elevated temperatures and humidity, which cause dimensional instability of the panels. The latter directly affect the performance of final products such as furniture, when they are used in situations of high relative humidity. Existing water-repellent formulations, such as paraffin, present limitations related to their non-renewable nature, cost and highest allowed added amount. Therefore, the aim of the present study was to test the suitability of renewable water repellents as alternative chemicals for enhancing the dimensional stability of MDF panels. A small amount of tall oil based formulations were used as water-repellent agents in the manufacturing of laboratory scale MDF. The effects on dimensional stability, internal bond strength and formaldehyde release of MDF were tested. The results indicated a good potential of tall oil as a bio-based substance of water repellent formulations for improving the dimensional stability of MDF.

Keywords: dimensional stability, medium density fiberboard, tall oil, urea formaldehyde

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Authors: Haile F. Darge, Hsieh C. Tsai

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The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

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Authors: Rosa L. Figueroa, Joselyn A. Hernández

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During the last couple of years, the Ministry of Health have been developing new health policies in order to regulate and improve in benefit of the patient the pharmaceutical system in our country. However, there are still some deficiencies in how medicines have been accessed, distributed, and sold. Therefore, it is necessary to empower the patient by offering new instances to improve access to drug information. This work introduces ‘the bioequivalent’ a medical drug search tool created to increase both diffusion and getting information about the therapeutic equivalence of medicines for the patient. The development of the search tool started with a study on the availability of sources of drug information accessible to the patient where advantages and disadvantages were analyzed. The information obtained was used to feed the functional design of the new tool. The design of the new tool shows an external interface that includes a header, body, sidebar and footer. The header has a menu containing ‘Home,’ ‘Who we are,’ and ‘Mission and vision.’ The Body contains the medical drug search tool, and the Sidebar is for the user logging in. It could be anonym, registered user, as well as, administrator. Anonym user could only use the tool. Registered users could add some information on existing medicines in the database; however, adding information will be restricted and limited to specific items and subject to administrator approval because the information added must be endorsed by the Chilean Public Health Institute. On the other hand, the administrator will have all the privileges, including creating or deleting drugs or information about them. The Bioequivalent was tested on different mobile devices, and no fails have been found. Moreover, a small survey was answered by ten people who tested the tool, and all of them agree that the tool was useful to get information about bioequivalent drugs, and they would recommend the tool to others. Nevertheless, an 80% of people who tested the tool says it was easy to use, and a 70% indicates that additional help is not required. These results are evidence that ‘the Bioequivalent’ may contribute to the knowledge about the therapeutic bioequivalence and bioequivalent drugs existing in Chile. As future work, the tool will be developed to make it available to the public for a first testing stage in a more massive scenario.

Keywords: collaborative database, bioequivalent drugs, search tool, web platform

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Authors: Olga Długosz, Jolanta Pulit-Prociak, Marcin Banach

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The paper presents a process to obtain glutathione-modified titanium oxide nanoparticles. The processes were carried out in a microwave radiation field. The influence of the molar ratio of glutathione to titanium oxide and the effect of the fold of NaOH vs. stoichiometric amount on the size of the formed TiO₂ nanoparticles was determined. The physicochemical properties of the obtained products were evaluated using dynamic light scattering (DLS), transmission electron microscope- energy-dispersive X-ray spectroscopy (TEM-EDS), low-temperature nitrogen adsorption method (BET), X-Ray Diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) microscopy methods. The size of TiO₂ nanoparticles was characterized from 30 to 336 nm. The release of titanium ions from the prepared products was evaluated. These studies were carried out using different media in which the powders were incubated for a specific time. These were water, SBF and Ringer's solution. The release of titanium ions from modified products is weaker compared to unmodified titanium oxide nanoparticles. The reduced release of titanium ions may allow the use of such modified materials as substances in drug delivery systems.

Keywords: titanium dioxide, nanoparticles, drug carrier, glutathione

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Authors: Olga Długosz, Jolanta Pulit-Prociak, Marcin Banach

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The paper presents a process to obtain glutathione-modified titanium oxide nanoparticles. The processes were carried out in a microwave radiation field. The influence of the molar ratio of glutathione to titanium oxide and the effect of the fold of NaOH vs. stoichiometric amount on the size of the formed TiO₂ nanoparticles was determined. The physicochemical properties of the obtained products were evaluated using dynamic light scattering (DLS), transmission electron microscope- energy-dispersive X-ray spectroscopy (TEM-EDS), low-temperature nitrogen adsorption method (BET), X-Ray Diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR) microscopy methods. The size of TiO₂ nanoparticles was characterized from 30 to 336 nm. The release of titanium ions from the prepared products was evaluated. These studies were carried out using different media in which the powders were incubated for a specific time. These were: water, SBF, and Ringer's solution. The release of titanium ions from modified products is weaker compared to unmodified titanium oxide nanoparticles. The reduced release of titanium ions may allow the use of such modified materials as substances in drug delivery systems.

Keywords: titanium dioxide, nanoparticles, drug carrier, glutathione

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Authors: Tomáš Nejedlý, Dominika Mrázková, Jitka Viktorová

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The blood-brain barrier (BBB) serves as a protective shield, preventing the entry of harmful substances into the central nervous system. On the other hand, it also restricts the transport of neuroactive drugs, such as antiepileptics, which mitigate epileptic seizures. Drug-resistant epilepsy is often associated with the overexpression of efflux transporters, including P-glycoprotein (P-gp) or multidrug resistance protein 1 (MRP1), on the BBB. The aim of this work is to find P-gp and MRP1 inhibitors derived from phytocannabinoids and terpenes. The work evaluates whether these compounds interact directly with P-gp or MRP1 by rhodamine 123 or fluorescein efflux assay. The effect of phytocannabinoids on the gene expression of these transporters is also studied using qPCR and Western blot. These transporters are found in BBB cells; however, we decided to use the human ovarian cancer cell line (A2780ADR) due to its overproduction of P-gp and malignant glioma cell line (U87) due to its overproduction of MRP1. The results showed that while terpenes suppressed the activity of efflux transporters, phytocannabinoids tended to decrease their expression. Terpenes demonstrated an average inhibition of 65%, surpassing phytocannabinoids, which exhibited an average inhibition of approximately 30%. Particularly noteworthy was the modulating effect of (-)-α-bisabolol with the highest activity among the compounds tested. Based on these findings, phytocannabinoids and terpenes emerge as promising natural candidates for addressing drug resistance linked to efflux transporters. Acknowledgment: The project was funded by the Grant No 22-20860S of The Czech Science Foundation.

Keywords: drug-resistant epilepsy, efflux transporters, multidrug resistance protein 1, P-glycoprotein, phytocannabinoids, terpens

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Authors: Nadim Zgheib, Sivaramakrishnan Balachandar

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We present results on the initial formation of ripples from an initially flattened erodible bed. We use direct numerical simulations (DNS) of turbulent open channel flow over a fixed sinusoidal bed coupled with hydrodynamic stability analysis. We use the direct forcing immersed boundary method to account for the presence of the sediment bed. The resolved flow provides the bed shear stress and consequently the sediment transport rate, which is needed in the stability analysis of the Exner equation. The approach is different from traditional linear stability analysis in the sense that the phase lag between the bed topology, and the sediment flux is obtained from the DNS. We ran 11 simulations at a fixed shear Reynolds number of 180, but for different sediment bed wavelengths. The analysis allows us to sweep a large range of physical and modelling parameters to predict their effects on linear growth. The Froude number appears to be the critical controlling parameter in the early linear development of ripples, in contrast with the dominant role of particle Reynolds number during the equilibrium stage.

Keywords: direct numerical simulation, immersed boundary method, sediment-bed interactions, turbulent multiphase flow, linear stability analysis

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Authors: Kyou Hee Shim, Hwa Sung Shin

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When a thrombolysis agent is administered to treat ischemic stroke, excessive reactive oxygen species are generated due to a sudden provision of oxygen and occurs secondary damage cell necrosis. Thus, it is necessary to administrate adjuvant as well as thrombolysis agent to protect and reduce damaged tissue. As cerebral blood vessels have specific structure called blood-brain barrier (BBB), it is not easy to transfer substances from blood to tissue. Therefore, development of a drug carrier is required to increase drug delivery efficiency to brain tissue. In this study, cyanobacterial pigment from the blue-green algae known for having neuroprotective effect as well as antioxidant effect was nasally administrated for bypassing BBB. In order to deliver cyanobacterial pigment efficiently, the nano-sized liposome was used as a carrier. Liposomes were coated with a positive charge of chitosan since negative residues are present at the nasal mucosa the first gateway of nasal administration. Characteristics of liposome including morphology, size and zeta potential were analyzed by transmission electron microscope (TEM) and zeta analyzer. As a result of cytotoxic test, the liposomes were not harmful. Also, being administered a drug to the ischemic stroke animal model, we could confirm that the pharmacological effect of the pigment delivered by chitosan coated liposome was enhanced compared to that of non-coated liposome. Consequently, chitosan coated liposome could be considered as an optimized drug delivery system for the treatment of acute ischemic stroke.

Keywords: ischemic stroke, cyanobacterial pigment, liposome, chitosan, nasal administration

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Authors: Maryam Parsian, Pelin Mutlu, Ufuk Gunduz

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Two-dimensional cell culture affords simplicity and low cost, but it has serious limitations; lacking cell-cell and cell-matrix interactions that are present in tissues. Cancer cells grown in 3D culture systems have distinct phenotypes of adhesion, growth, migration, invasion as well as profiles of gene and protein expression. These interactions cause the 3D-cultured cells to acquire morphological and cellular characteristics relevant to in vivo tumors. Palbociclib is a chemotherapeutic agent for the treatment of ER-positive and HER-negative metastatic breast cancer. Poly-amidoamine (PAMAM) dendrimer is a well-defined, special three-dimensional structure and has a multivalent surface and internal cavities that can play an essential role in drug delivery systems. In this study, palbociclib is loaded onto the magnetic PAMAM dendrimer. Hanging droplet method was used in order to form 3D spheroids. The possible toxic effects of both free drug and drug loaded nanoparticles were evaluated in 2D and 3D MCF-7, MD-MB-231 and SKBR-3 breast cancer cell culture models by performing MTT cell viability and Alamar Blue assays. MTT analysis was performed with six different doses from 1000 µg/ml to 25 µg/ml. Drug unloaded PAMAM dendrimer did not demonstrate significant toxicity on all breast cancer cell lines. The results showed that 3D spheroids are clearly less sensitive than 2D cell cultures to free palbociclib. Also, palbociclib loaded PAMAM dendrimers showed more toxic effect than free palbociclib in all cell lines at 2D and 3D cultures. The results suggest that the traditional cell culture method (2D) is insufficient for mimicking the actual tumor tissue. The response of the cancer cells to anticancer drugs is different in the 2D and 3D culture conditions. This study showed that breast cancer cells are more resistant to free palbociclib in 3D cultures than in 2D cultures. However, nanoparticle loaded drugs can be more cytotoxic when compared to free drug.

Keywords: 2D and 3D cell culture, breast cancer, palbociclibe, PAMAM magnetic nanoparticles

Procedia PDF Downloads 140

Authors: Bouami Hind, Millot Patrick

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The implementation of automated devices in life-critical systems such as hospitals can bring a new set of challenges related to automation malfunctions. While automation has been identified as great leverage for the medication dispensing system’s security and efficiency, it also increases the complexity of the organization. In particular, the installation and operation stage of automated devices can be complex when malfunctions related to automated systems occur. This paper aims to document operators’ situation awareness about the malfunctions of automated drug delivery systems (ADCs) during their implementation through Saint Brieuc hospital’s feedback. Our evaluation approach has been deployed in Saint Brieuc hospital center’s pharmacy, which has been equipped with automated nominative drug dispensing systems since January of 2021. The analysis of Saint Brieuc hospital center pharmacy’s automation revealed numerous malfunctions related to the implementation of Automated Delivery Cabinets. It appears that the targeted performance is not reached in the first year of implementation in this case study. Also, errors have been collected in patients' automated treatments’ production such as lack of drugs in pill boxes or nominative carnets, excess of drugs, wrong location of the drug, drug blister damaged, non-compliant sachet, or ticket errors. Saint Brieuc hospital center’s pharmacy is doing a tremendous job of setting up and monitoring performance indicators from the beginning of automation and throughout ADC’s operation to control ADC’s malfunctions and meet the performance targeted by the hospital. Health professionals, including pharmacists, biomedical engineers and directors of work, technical services and safety, are heavily involved in an automation project. This study highlights the importance of the evaluation of ADCs’ performance throughout the implementation process and the hospital’s team involvement in automation supervision and management.

Keywords: life-critical systems, situation awareness, automated delivery cabinets, implementation, risks and malfunctions

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Authors: Farhan Sohail, Gul Shahnaz Irshad Hussain, Shoaib Sarwar, Ibrahim Javed, Zajif Hussain, Akhtar Nadhman

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The present study was aimed to develop a hybrid nanocarrier (NC) system with enhanced membrane permeability, bioavailability and targeted delivery of Docetaxel (DTX) in breast cancer. Hybrid NC’s based on folic acid (FA) grafted thiolated chitosan (TCS) enveloped liposomes were prepared with DTX and evaluated in-vitro and in-vivo for their enhanced permeability and bioavailability. Physicochemical characterization of NC’s including particle size, morphology, zeta potential, FTIR, DSC, PXRD, encapsulation efficiency and drug release from NC’s was determined in vitro. Permeation enhancement and p-gp inhibition were performed through everted sac method on freshly excised rat intestine which indicated that permeation was enhanced 5 times as compared to pure DTX and the hybrid NC’s were strongly able to inhibit the p-gp activity as well. In-vitro cytotoxicity and tumor targeting was done using MDA-MB-231 cell line. The stability study of the formulations performed for 3 months showed the improved stability of FA-TCS enveloped liposomes in terms of its particles size, zeta potential and encapsulation efficiency as compared to TCS NP’s and liposomes. The pharmacokinetic study was performed in vivo using rabbits. The oral bioavailability and AUC0-96 was increased 10.07 folds with hybrid NC’s as compared to positive control. Half-life (t1/2) was increased 4 times (58.76 hrs) as compared to positive control (17.72 hrs). Conclusively, it is suggested that FA-TCS enveloped liposomes have strong potential to enhance permeability and bioavailability of hydrophobic drugs after oral administration and tumor targeting.

Keywords: docetaxel, coated liposome, permeation enhancement, oral bioavailability

Procedia PDF Downloads 399

Authors: Ali Ayatic, Emad Mozaffari, Bahareh Tanhaei, Maryam Khajenoori, Saeedeh Movaghar Khoshkho, Ali Ayati

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The abuse of antibiotics, such as tetracycline (TC), is a great global threat to people and the use of topical antibiotics is a promising tact that can help to solve this problem. Antibiotic therapy is often appropriate and necessary for acute wound infections, while topical tetracycline can be highly efficient in improving the wound healing process in diabetics. Due to the advantages of drug-loaded hydrogels as wound dressing, such as ease of handling, high moisture resistance, excellent biocompatibility, and the ability to activate immune cells to speed wound healing, it was found as an ideal wound treatment. In this work, the tetracycline-loaded hydrogels combining agar (AG) and κ-carrageenan (k-CAR) as polymer materials were prepared, in which span60 surfactant was introduced inside as a drug carrier. The Field Emission Scanning Electron Microscopes (FESEM) and Fourier-transform infrared spectroscopy (FTIR) techniques were employed to provide detailed information on the morphology, composition, and structure of fabricated drug-loaded hydrogels and their mechanical properties, and hydrogel permeability to water vapor was investigated as well. Two types of gram-negative and gram-positive bacteria were used to explore the antibacterial properties of prepared tetracycline-contained hydrogels. Their swelling and drug release behavior was studied using the changing factors such as the ratio of polysaccharides (MAG/MCAR), the span60 surfactant concentration, potassium chloride (KCl) concentration and different release media (deionized water (DW), phosphate-buffered saline (PBS), and simulated wound fluid (SWF)) at different times. Finally, the kinetic behavior of hydrogel swelling was studied. Also, the experimental data of TC release to DW, PBS, and SWF using various mathematical models such as Higuchi, Korsmeyer-Peppas, zero-order, and first-order in the linear and nonlinear modes were evaluated.

Keywords: drug release, hydrogel, tetracycline, wound healing

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Authors: H. Aksas, S. Boughrara, K. Louhab

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The goal of this study was the use of life cycle assessment (LCA) methodology to assess the environmental impact of pharmaceutical product (four kinds of syrup form and tree kinds of pomade form), which are produced in one leader manufactory in Algeria town that is SAIDAL Company. The impacts generated have evaluated using SimpaPro7.1 with CML92 Method for syrup form and EPD 2007 for pomade form. All impacts evaluated have compared between them, with determination of the compound contributing to each impacts in each case. Data needed to conduct Life Cycle Inventory (LCI) came from this factory, by the collection of theoretical data near the responsible technicians and engineers of the company, the practical data are resulting from the assay of pharmaceutical liquid, obtained at the laboratories of the university. This data represent different raw material imported from European and Asian country necessarily to formulate the drug. Energy used is coming from Algerian resource for the input. Outputs are the result of effluent analysis of this factory with different form (liquid, solid and gas form). All this data (input and output) represent the ecobalance.

Keywords: pharmaceutical product, drug residues, LCA methodology, environmental impacts

Procedia PDF Downloads 239

Authors: C. E. Madubueze, S. C. Madubueze, S. Ajama

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Cholera is a disease that is predominately common in developing countries due to poor sanitation and overcrowding population. In this paper, a deterministic model for the dynamics of cholera is developed and control measures such as health educational message, therapeutic treatment, and vaccination are incorporated in the model. The effective reproduction number is computed in terms of the model parameters. The existence and stability of the equilibrium states, disease free and endemic equilibrium states are established and showed to be locally and globally asymptotically stable when R0 < 1 and R0 > 1 respectively. The existence of backward bifurcation of the model is investigated. Furthermore, numerical simulation of the model developed is carried out to show the impact of the control measures and the result indicates that combined control measures will help to reduce the spread of cholera in the population

Keywords: backward bifurcation, cholera, equilibrium, dynamics, stability

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Authors: Nurudeen Oluwasola Lasisi, Abdulkareem Afolabi Ibrahim

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Newcastle disease is an infection of domestic poultry and other bird species with virulent Newcastle disease virus (NDV). In this paper, we study the dynamics of modeling the Newcastle disease virus (NDV) using a novel quarantine-adjusted incidence. We do a comparison of Vaccination, linear incident rate, and novel quarantine adjusted incident rate in the models. The dynamics of the models yield disease free and endemic equilibrium states. The effective reproduction numbers of the models are computed in order to measure the relative impact for the individual bird or combined intervention for effective disease control. We showed the local and global stability of endemic equilibrium states of the models, and we found that stability of endemic equilibrium states of models are globally asymptotically stable if the effective reproduction numbers of the models equations are greater than a unit.

Keywords: effective reproduction number, endemic state, mathematical model, Newcastle disease virus, novel quarantine-adjusted incidence, stability analysis

Procedia PDF Downloads 232

Authors: Abubakar Sadiq Mensah

Abstract:

The Knowledge of the population growth of a nation is paramount to national planning. The population of a place is studied and a model developed over a period of time, Matrices is used to form model for population growth. The eigenvalue ƛ of the matrix A and its corresponding eigenvector X is such that AX = ƛX is calculated. The stable age distribution of the population is obtained using the eigenvalue and the characteristic polynomial. Hence, estimation could be made using eigenvalues and eigenvectors.

Keywords: eigenvalues, eigenvectors, population, growth/stability

Procedia PDF Downloads 505